A unilateral experimental neuropathy is produced in the sciatic nerve of rats. The postoperative behavior of these animals indicates that the nerve injury produces disordered pain sensations like those that are seen in humans with nerve injuries due to trauma or disease. The symptoms of neuropathic pain in these animals include hyperalgesia, allodynia, and spontaneous pain. We have shown that the nerve injury evokes large changes in the neurochemistry of small diameter, primary afferent neurons whose axons travel in the injured nerve. The changes begin within 5-10 days and persist for 2-3 months. The changes seen to date are decreases in the levels of substance P, calcitonin gene-related peptide and fluoride-resistant acid phosphatase. The decreases have been seen in the neurons; somata in the dorsal root ganglia and also in their terminal arbors in spinal dorsal horn laminae I- II and V. An additional change has been noted in intrinsic spinal neurons. Within days of the nerve injury, there is a large increase in spinal levels of the opioid peptide, dynorphin. This increase is initially found in neurons in laminae I and V-VI. By 10 days, however, only the deeper cells can be detected. Examination of toluidine blue-stained thin sections has shown that many small neurons in laminae I-III have the increased cytoplasmic and nucleo-plasmic staining density that precedes neuronal degeneration. The symptoms of disordered pain sensation are detectable 2 days after the nerve injury. Nerve function has been studied during the prodromal period (1 day old injuries) and we have found marked abnormalities. A very large majority of the nerve's myelinated axons cannot conduct impulses across the injured region, but nearly all of the unmyelinated fibers conduct normally. About 25% of the myelinated fibers emit spontaneous, ectopic discharges that are exacerbated by gallamine triehiodide. It is known from other experiments that the gallamine effect reflects an abnormality in voltage-sensitive potassium conductance and this, in turn, is a likely mechanisms for the production of the spontaneous discharge.